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Estimated plasma osmolarity and risk of end-stage kidney disease in patients with IgA nephropathy

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Abstract

Background

Several experimental studies have indicated that increased plasma osmolarity caused by recurrent dehydration is involved in kidney injury via a mechanism, mediated by vasopressin secretion and activation of the aldose reductase pathway. Epidemiologic evidence linking increased plasma osmolarity and the onset of end-stage kidney disease (ESKD), in patients with primary glomerulonephritis, is lacking.

Methods

We retrospectively examined 663 patients with IgA nephropathy (IgAN) diagnosed by kidney biopsy and evaluated the association between estimated plasma osmolarity and ESKD prevalence, using a Cox proportional hazards model.

Results

During follow-up (median 80.4 months; interquartile range 22.2–120.1), 73 patients developed ESKD. In a baseline survey, plasma osmolarity was correlated negatively with the mean value of the estimated glomerular filtration rate, but correlated positively with the mean value of urinary protein excretion, systolic blood pressure, and pathologic severity of extracapillary proliferation, in addition to tissue fibrosis and sclerosis. The incidence rate of ESKD increased linearly with increase in plasma osmolarity (P < 0.05 for trend). In multivariate analyses, plasma osmolarity was an independent risk factor for ESKD (hazard ratio for each increment of 5 mOsm/kg in plasma osmolarity 1.56; 95% confidence interval 1.18–2.07) even after adjustment for potential confounders.

Conclusions

Increased plasma osmolarity was associated significantly with an increased risk of ESKD in patients with IgAN. Maintenance of plasma osmolarity by appropriate control of the balance between salt and water may contribute to kidney protection.

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References

  1. Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, et al. Chronic kidney disease: global dimension and perspectives. Lancet. 2013;382(9888):260–72. https://doi.org/10.1016/S0140-6736(13)60687-X.

    Article  PubMed  Google Scholar 

  2. Lv J, Zhang H, Zhou Y, Li G, Zou W, Wang H. Natural history of immunoglobulin A nephropathy and predictive factors of prognosis: a long-term follow up of 204 cases in China. Nephrology (Carlton). 2008;13(3):242–6. https://doi.org/10.1111/j.1440-1797.2007.00898.x.

    Article  Google Scholar 

  3. D'Amico G. The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med. 1987;64(245):709–27.

    CAS  PubMed  Google Scholar 

  4. Koyama A, Igarashi M, Kobayashi M. Natural history and risk factors for immunoglobulin A nephropathy in Japan. Research Group on Progressive Renal Diseases. Am J Kidney Dis. 1997;29(4):526–32.

    Article  CAS  Google Scholar 

  5. Glaser J, Lemery J, Rajagopalan B, Diaz HF, Garcia-Trabanino R, Taduri G, et al. Climate change and the emergent epidemic of CKD from heat stress in rural communities: the case for heat stress nephropathy. Clin J Am Soc Nephrol. 2016;11(8):1472–83. https://doi.org/10.2215/CJN.13841215.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Torres C, Aragon A, Gonzalez M, Lopez I, Jakobsson K, Elinder CG, et al. Decreased kidney function of unknown cause in Nicaragua: a community-based survey. Am J Kidney Dis. 2010;55(3):485–96. https://doi.org/10.1053/j.ajkd.2009.12.012.

    Article  PubMed  Google Scholar 

  7. Raines N, Gonzalez M, Wyatt C, Kurzrok M, Pool C, Lemma T, et al. Risk factors for reduced glomerular filtration rate in a Nicaraguan community affected by Mesoamerican nephropathy. MEDICC Rev. 2014;16(2):16–22.

    Article  Google Scholar 

  8. Garcia-Trabanino R, Jarquin E, Wesseling C, Johnson RJ, Gonzalez-Quiroz M, Weiss I, et al. Heat stress, dehydration, and kidney function in sugarcane cutters in El Salvador–a cross-shift study of workers at risk of Mesoamerican nephropathy. Environ Res. 2015;142:746–55. https://doi.org/10.1016/j.envres.2015.07.007.

    Article  CAS  PubMed  Google Scholar 

  9. Cirillo P, Gersch MS, Mu W, Scherer PM, Kim KM, Gesualdo L, et al. Ketohexokinase-dependent metabolism of fructose induces proinflammatory mediators in proximal tubular cells. J Am Soc Nephrol. 2009;20(3):545–53. https://doi.org/10.1681/ASN.2008060576.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Johnson RJ, Rodriguez-Iturbe B, Roncal-Jimenez C, Lanaspa MA, Ishimoto T, Nakagawa T, et al. Hyperosmolarity drives hypertension and CKD–water and salt revisited. Nat Rev Nephrol. 2014;10(7):415–20. https://doi.org/10.1038/nrneph.2014.76.

    Article  CAS  PubMed  Google Scholar 

  11. Kuwabara M, Hisatome I, Roncal-Jimenez CA, Niwa K, Andres-Hernando A, Jensen T, et al. Increased serum sodium and serum osmolarity are independent risk factors for developing chronic kidney disease; 5 year cohort study. PLoS ONE. 2017;12(1):e0169137. https://doi.org/10.1371/journal.pone.0169137.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bhagat CI, Garcia-Webb P, Fletcher E, Beilby JP. Calculated vs measured plasma osmolalities revisited. Clin Chem. 1984;30(10):1703–5.

    Article  CAS  Google Scholar 

  13. Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Hara S, et al. Estimation of glomerular filtration rate by the MDRD study equation modified for Japanese patients with chronic kidney disease. Clin Exp Nephrol. 2007;11(1):41–50. https://doi.org/10.1007/s10157-006-0453-4.

    Article  PubMed  Google Scholar 

  14. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53(6):982–92. https://doi.org/10.1053/j.ajkd.2008.12.034.

    Article  CAS  PubMed  Google Scholar 

  15. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics. 1976;58(2):259–63.

    CAS  PubMed  Google Scholar 

  16. Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin N Am. 1987;34(3):571–90.

    Article  CAS  Google Scholar 

  17. Katafuchi R, Ninomiya T, Mizumasa T, Ikeda K, Kumagai H, Nagata M, et al. The improvement of renal survival with steroid pulse therapy in IgA nephropathy. Nephrol Dial Transplant. 2008;23(12):3915–20. https://doi.org/10.1093/ndt/gfn394.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yamamoto Y, Hiki Y, Nakai S, Yamamoto K, Takahashi K, Koide S, et al. Comparison of effective impact among tonsillectomy alone, tonsillectomy combined with oral steroid and with steroid pulse therapy on long-term outcome of immunoglobulin A nephropathy. Clin Exp Nephrol. 2013;17(2):218–24. https://doi.org/10.1007/s10157-012-0679-2.

    Article  CAS  PubMed  Google Scholar 

  19. Cattran DC, Coppo R, Cook HT, Feehally J, Roberts IS, Troyanov S, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int. 2009;76(5):534–45. https://doi.org/10.1038/ki.2009.243.

    Article  PubMed  Google Scholar 

  20. Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, et al. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009;76(5):546–56. https://doi.org/10.1038/ki.2009.168.

    Article  PubMed  Google Scholar 

  21. Jayasumana C, Gunatilake S, Senanayake P. Glyphosate, hard water and nephrotoxic metals: are they the culprits behind the epidemic of chronic kidney disease of unknown etiology in Sri Lanka? Int J Environ Res Public Health. 2014;11(2):2125–47. https://doi.org/10.3390/ijerph110202125.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Wesseling C, van de Wendel JB, Crowe J, Rittner R, Sanati NA, Hogstedt C, et al. Mesoamerican nephropathy: geographical distribution and time trends of chronic kidney disease mortality between 1970 and 2012 in Costa Rica. Occup Environ Med. 2015;72(10):714–21. https://doi.org/10.1136/oemed-2014-102799.

    Article  PubMed  Google Scholar 

  23. Laux TS, Barnoya J, Guerrero DR, Rothstein M. Dialysis enrollment patterns in Guatemala: evidence of the chronic kidney disease of non-traditional causes epidemic in Mesoamerica. BMC Nephrol. 2015;16:54. https://doi.org/10.1186/s12882-015-0049-x.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Abraham G, Varughese S, Thandavan T, Iyengar A, Fernando E, Naqvi SA, et al. Chronic kidney disease hotspots in developing countries in South Asia. Clin Kidney J. 2016;9(1):135–41. https://doi.org/10.1093/ckj/sfv109.

    Article  PubMed  Google Scholar 

  25. Orantes CM, Herrera R, Almaguer M, Brizuela EG, Hernandez CE, Bayarre H, et al. Chronic kidney disease and associated risk factors in the Bajo Lempa region of El Salvador: Nefrolempa study, 2009. MEDICC Rev. 2011;13(4):14–22.

    Article  Google Scholar 

  26. Herrera R, Orantes CM, Almaguer M, Alfonso P, Bayarre HD, Leiva IM, et al. Clinical characteristics of chronic kidney disease of nontraditional causes in Salvadoran farming communities. MEDICC Rev. 2014;16(2):39–48.

    Article  Google Scholar 

  27. Roncal Jimenez CA, Ishimoto T, Lanaspa MA, Rivard CJ, Nakagawa T, Ejaz AA, et al. Fructokinase activity mediates dehydration-induced renal injury. Kidney Int. 2014;86(2):294–302. https://doi.org/10.1038/ki.2013.492.

    Article  CAS  PubMed  Google Scholar 

  28. Bankir L, Bouby N, Ritz E. Vasopressin: a novel target for the prevention and retardation of kidney disease? Nat Rev Nephrol. 2013;9(4):223–39. https://doi.org/10.1038/nrneph.2013.22.

    Article  CAS  PubMed  Google Scholar 

  29. Bardoux P, Martin H, Ahloulay M, Schmitt F, Bouby N, Trinh-Trang-Tan MM, et al. Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: study in vasopressin-deficient Brattleboro rats. Proc Natl Acad Sci USA. 1999;96(18):10397–402.

    Article  CAS  Google Scholar 

  30. Assimacopoulos-Jeannet F, McCormack JG, Jeanrenaud B. Vasopressin and/or glucagon rapidly increases mitochondrial calcium and oxidative enzyme activities in the perfused rat liver. J Biol Chem. 1986;261(19):8799–804.

    CAS  PubMed  Google Scholar 

  31. Bardoux P, Bichet DG, Martin H, Gallois Y, Marre M, Arthus MF, et al. Vasopressin increases urinary albumin excretion in rats and humans: involvement of V2 receptors and the renin-angiotensin system. Nephrol Dial Transplant. 2003;18(3):497–506.

    Article  CAS  Google Scholar 

  32. Wijkstrom J, Leiva R, Elinder CG, Leiva S, Trujillo Z, Trujillo L, et al. Clinical and pathological characterization of Mesoamerican nephropathy: a new kidney disease in Central America. Am J Kidney Dis. 2013;62(5):908–18. https://doi.org/10.1053/j.ajkd.2013.05.019.

    Article  PubMed  Google Scholar 

  33. Shapiro L, Dinarello CA. Osmotic regulation of cytokine synthesis in vitro. Proc Natl Acad Sci USA. 1995;92(26):12230–4. https://doi.org/10.1073/pnas.92.26.12230.

    Article  CAS  PubMed  Google Scholar 

  34. Shapiro L, Dinarello CA. Hyperosmotic stress as a stimulant for proinflammatory cytokine production. Exp Cell Res. 1997;231(2):354–62. https://doi.org/10.1006/excr.1997.3476.

    Article  CAS  PubMed  Google Scholar 

  35. Ying WZ, Sanders PW. Dietary salt enhances glomerular endothelial nitric oxide synthase through TGF-beta1. Am J Physiol. 1998;275(1):F18–F24. https://doi.org/10.1152/ajprenal.1998.275.1.F18.

    Article  CAS  PubMed  Google Scholar 

  36. Gu JW, Anand V, Shek EW, Moore MC, Brady AL, Kelly WC, et al. Sodium induces hypertrophy of cultured myocardial myoblasts and vascular smooth muscle cells. Hypertension. 1998;31(5):1083–7. https://doi.org/10.1161/01.hyp.31.5.1083.

    Article  CAS  PubMed  Google Scholar 

  37. Tanaka S, Ninomiya T, Fujisaki K, Yoshida H, Nagata M, Masutani K, et al. The Fukuoka Kidney disease Registry (FKR) Study: design and methods. Clin Exp Nephrol. 2017;21(3):465–73. https://doi.org/10.1007/s10157-016-1294-4.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank the investigators at the participating institutions: Tetsuhiko Yoshida, M.D., Hirofumi Ikeda, M.D., Ph.D., Takashi Inenaga, M.D., Akinori Nagashima, M.D., Ph.D., and Tadashi Hirano, M.D. We also thank Arshad Makhdum, PhD, from Edanz Group (https://www.edanzediting.com/ac) for editing a draft of this manuscript. This study was supported by Grants-in-Aid for Scientific Research (18K17405) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Funding

This study was supported by Grants-in-Aid for Scientific Research (18K17405) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Shigeru Tanaka, Toshiaki Nakano, Akihiro Tsuchimoto & Takanari Kitazono

  2. Department of Internal Medicine, Fukuoka Dental College, Fukuoka, Japan

    Masanori Tokumoto & Hiroaki Ooboshi

  3. Department of Nephrology and Rheumatology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan

    Kosuke Masutani

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  1. Shigeru Tanaka
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Contributions

Shigeru Tanaka contributed to the study design, acquisition of data, statistical analyses, interpretation of data, and drafting of the manuscript. Toshiaki Nakano contributed to the funding, acquisition of data, and critical revision of the manuscript. Kosuke Masutani and Akihiro Tsuchimoto contributed to the pathologic evaluation of kidney biopsies, and critical revision of the manuscript. Masanori Tokumoto, Hiroaki Ooboshi and Takanari Kitazono contributed to the critical revision of the manuscript and study supervision. All authors provided critical reviews of the draft and approved the final version.

Corresponding author

Correspondence to Toshiaki Nakano.

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The authors have declared that no conflict of interest exists.

Human and animal rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board (IRB) at which the studies were conducted (IRB approval number 469-8 in Kyushu University, Fukuoka, Japan) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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The ethics committee of all participating institutions granted approval to waive requirement for written, informed consent because of the retrospective nature of the present study.

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Tanaka, S., Nakano, T., Tokumoto, M. et al. Estimated plasma osmolarity and risk of end-stage kidney disease in patients with IgA nephropathy. Clin Exp Nephrol 24, 910–918 (2020). https://doi.org/10.1007/s10157-020-01919-3

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